Acute alcohol intoxication is a significant health problem in the United States and contributes to an increased risk of traumatic injury, accounting for the majority of alcohol-related disorders encountered in emergency rooms [17,41]. Frequent drinkers, reported as those individuals who drink on a weekly basis, are six times more likely to be admitted to the emergency room than individuals who drink infrequently [7]. Nearly 40% of injured patients admitted to the ER have intoxicating BAC greater than 80 mg/dL [7,22,38,41]. Intoxicated trauma patients often present with increased initial injury severity compared to non-intoxicated patients [18,38]. In addition, these patients typically require a significantly greater frequency of interventions in the hospital such as endotracheal intubations, placement of intracranial monitoring devices, and greater use of diagnostic peritoneal lavage [18].
One particularly problematic outcome that can occur with acute alcohol intoxication is aggravated hemodynamic instability following hemorrhage [33]. Intoxicated trauma patients are significantly more hypotensive upon arrival to the emergency department compared to non-intoxicated patients. Clinical studies have demonstrated that this low mean arterial blood pressure (MABP) in alcohol-intoxicated patients is a predictor of poor outcomes [3,16,41]. In addition, these patients require significantly greater volumes of intravenous crystalloid resuscitative fluids and blood products, despite the fact that there is no increase in severity of injury or difference in the international normalized ratio (used in determining the time blood takes to clot) compared to non-intoxicated patients [3,12,33]. Several studies have postulated that an impaired baroreceptor reflex or associated neural, endocrine, and metabolic mechanisms that control vascular tone may be responsible for this increased hypotension [14,24,26,27]. This is supported by the findings that: 1) significantly less blood from alcohol-intoxicated rats is required to produce the same hypotensive pressure during a fixed-pressure hemorrhage; and 2) with fixed-volume hemorrhage, alcohol-intoxicated rats are significantly more hypotensive following equal volumes of removed blood [24,27]. The elevations in plasma levels of epinephrine, norepinephrine, and arginine vasopressin to fixed-pressure hemorrhage are all significantly blunted in alcohol intoxicated rats compared to non-intoxicated animals [26]. However, more recent studies have shown that sympathetic control of blood pressure and acetylcholine-induced vasodilation are not impaired by alcohol intoxication [23,25]. Intracerebroventricular administration of choline, a precursor of the preganglionic neurotransmitter acetylcholine, is unable to improve hemodynamic and neuroendocrine counter-responses to hemorrhagic shock in alcohol-intoxicated rats [23]. Furthermore, studies using isolated aorta and mesenteric arteries of intoxicated and non-intoxicated rats show that this impaired hemodynamic counter-regulation to hemorrhage is not due to a decrease in responsiveness of blood vessels to vasoconstrictors like phenylephrine, or vasodilators like acetylcholine [25].